N-WASP Is Required for Stabilization of Podocyte Foot Processes

Abstract

Alteration of cortical actin structures is the common final pathway leading to podocyte foot process effacement and proteinuria. The molecular mechanisms that safeguard podocyte foot process architecture and maintain the three-dimensional actin network remain elusive. Here, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP), which promotes actin nucleation, is required to stabilize podocyte foot processes. Mice lacking N-WASP specifically in podocytes were born with normal kidney function but developed significant proteinuria 3 weeks after birth, suggesting an important role for N-WASP in maintaining foot processes. In addition, inducing deletion of N-WASP in adult mice resulted in severe proteinuria and kidney failure. Electron microscopy showed an accumulation of electron-dense patches of actin and strikingly altered morphology of podocyte foot processes. Although basic actin-based processes such as cell migration were not affected, primary cultures of N-WASP-deficient podocytes revealed significant impairment of dynamic actin reorganization events, including the formation of circular dorsal ruffles. Taken together, our findings suggest that N-WASP-mediated actin nucleation of branched microfilament networks is specifically required for the maintenance of foot processes, presumably sustaining the mechanical resistance of the filtration barrier.

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Serum with phospholipase A2 receptor autoantibodies interferes with podocyte adhesion to collagen

“…The attachment of mock-transfected HEK cells was significantly higher on the uncoated surface compared with the collagencoated surface. There is little information regarding the activity of podosomes in podocytes, but a recent publication reported that N-WASP, a crucial and characteristic regulator involved in the formation of podosomes [20], is also important in maintaining the podocyte foot processes [21]. It indicates that HEK cells, at least in certain experimental conditions, do not attach very well to collagen.…”